Method for modifying an organic composition

ABSTRACT

There is provided a process for modifying a first organic composition comprising (i) at least one first solvent, (ii) at least one solute, and (iii) optionally, at least one second solvent to produce a modified organic composition in which the concentration of the at least one first solvent is reduced and the concentration of the at least one second solvent is increased, comprising the steps of: (a) providing a selectively permeable membrane having a first surface and a second surface; (b) transferring a portion of the first solvent and optionally a portion of the solute from the first surface to the second surface across the membrane by contacting the first organic composition with the first surface, wherein the pressure at the first surface is greater than the pressure at the second surface, and wherein the membrane is a selectively permeable membrane such that the membrane rejection (R) of the solute is greater than 0%; (c) adding a portion of the second solvent to the organic composition retained at the first surface of the membrane.

The present invention relates to solvent exchange processes. In anotheraspect, it relates to concentration of organic solutes in organicsolvents using solvent resistant nanofiltration membranes. In anotheraspect it relates to addition of one or more solvents to an organicliquid containing solutes and solvents to change the composition of themixture. In particular the process comprises utilising solvent resistantnanofiltration membranes to alter the mixture of solvents in which oneor more solutes is dissolved.

Many organic syntheses take place through multiple sequential stages.These stages may comprise for example sequential reaction stages, orreaction stages followed by purification stages. In many cases theorganic molecules which are the products of a first stage are presentdissolved as solutes in a first solvent or a first solvent mixture atthe completion of the first stage. The second, following stage maycomprise for example purification or another reaction stage. In manycases, this second stage may require that the products of the firststage are dissolved in a second solvent or a second solvent mixturedifferent to that used in the first stage. Altering the solvent orsolvent mixture composition from the first solvent or solvent mixture tothe second solvent or solvent mixture requires a solvent exchangeoperation.

In general, two important cases can be identified for solvent exchangeoperations, depending on the boiling points of the first solvent and thesecond solvent. The first case is when the first solvent has a lowerboiling point than both the second solvent and the solute. In this case,distillation can be employed to remove aliquots of the first solvent.Aliquots of the second solvent can be added to replace the first solventas it is boiled off, and the process will eventually result in a mixturecomprising the solute dissolved in the second solvent. The second caseis when the first solvent has a higher boiling point than the secondsolvent, but lower than the solute. Here it is not possible to exchangesolvents by progressively distilling and adding the second solvent, asthe condensed distillate will tend to be rich in the second solvent andso the first solvent will not be removed. To overcome this difficulty,it may be necessary to use vacuum distillation coupled with a scrapedsurface drier to remove essentially all the first solvent prior toadding any of the second solvent. This process may be time consuming andmay result in the solutes being exposed to temperatures higher thantheir thermal decomposition temperatures, which may cause loss ofproducts through thermal decomposition. It can be understood by oneskilled in the art that the same general problems exist when instead ofhaving a first solvent and a second solvent, mixtures of severalsolvents are present in the first stage, or in the second stage, or inboth. Indeed in systems involving mixed solvents azeotropes may formwhich further complicate distillation as a means to effect solventexchange.

Membrane processes are well known in the art of separation science, andcan be applied to a range of separations of species of varying molecularweights in liquid and gas phases (see for example “Membrane Technology”in Kirk Othmer Encyclopedia of Chemical Technology, 4^(th) Edition 1993,Vol 16, pages 135-193). Nanofiltration is a membrane process utilisingmembranes whose pores are in the range 0.5-5 nm, and which have MWcutoffs of 200-1000 Daltons. Nanofiltration has been widely applied tofiltration of aqueous fluids, but due to a lack of suitable solventstable membranes has not been widely applied to separation of solutes inorganic solvents.

U.S. Pat. Nos. 5,205,934 and 5,265,734 describe processes for producingcomposite nanofiltration membranes which comprise a layer of siliconeimmobilised onto a support, preferably a polyacrylonitrile support.These composite membranes are claimed to be solvent stable and areclaimed to have utility for separation of high molecular weight solutes,including organometallic catalyst complexes, from organic solvents. Theperformance of these composite membranes in separating solutes frommethanol solutions has been described in the open literature(“Nanofiltration studies of larger organic microsolutes in methanolsolutions”, Whu J. A., Baltzis B. C., Sirkar K. K. Journal of MembraneScience 170 (2000) pages 159-172), and their performance in permeationof pure solvent phases has also been reported (“Effect of solventproperties on permeate flow through nanofiltration membranes. PartI—investigation of parameters affecting solvent flux” Machado D. R.,Hasson D., Semiat R. Journal of Membrane Science 163 (1999) pages93-102). The application of these membranes to recovering solvents fromchromatographic systems is described in U.S. Pat. No. 5,676,832.

U.S. Pat. No. 5,264,166 describes processes for the production ofasymmetric polyimide membranes which are claimed to be stable insolvents such as toluene, benzene, xylene, methyl ethyl ketone (MEK) andmethyl iso butyl ketone (MIBK). These asymmetric membranes are claimedto have utility for the separation of low molecular weight organicmaterials with a molecular weight in the range 300-400 from solventswith molecular weight of around 100. The application of these membranesto solvent recovery from lube oil filtrates are described in U.S. Pat.Nos. 5,360,530; 5,494,566; 5,651,877, and in the open literature in“Solvent recovery from lube oil filtrates with a polyimide membrane”White L. S., Nitsch A. R. Journal of Membrane Science 179 (2000) pages267-274.

The use of membranes to separate catalysts from organic solvents isknown in the art and has been described in the open literature. “ReverseOsmosis in Homogeneous Catalysis” Gosser L. W., Knoth W. H., Parshall G.W. Journal of Molecular Catalysis 2 (1977) pages 253-263 describesexperiments using selectively permeable polyimide membranes to separatesoluble transition metal catalysts from reaction mixtures by reverseosmosis. “Modeling of nanofiltration—assisted organic synthesis”, J. A.Whu, B. C. Baltzis, K. K. Sirkar, Journal of Membrane Science, 163(1999) 319-331 describes modelling used to investigate the potentialapplication of solvent stable nanofiltration membranes to catalystseparation and recycle.

The patent literature also describes the use of membranes to separatecatalysts from organic solvents. U.S. Pat. No. 5,174,899 discloses theseparation of organometallic compounds and/or metal carbonyls from theirsolutions in organic media with the aid of semi-permeable membranes madeof aromatic polyamides.

U.S. Pat. Nos. 5,215,667; 5,288,818 5,298,669 and 5,395,979 describe theuse of a hydrophobic membrane to separate water-soluble noble metalionic phosphine ligand complex catalysts from aldehyde containinghydroformylation reaction mediums comprising aqueous solutions,emulsions or suspensions of said catalysts. U.S. Pat. No. 5,681,473describes the application of solvent-resistant composite membranes toseparation of organic-solubilised rhodium-organophosphite complexcatalyst and free organophosphite ligand from a homogeneous non-aqueoushydroformylation reaction mixture.

In the above prior art, membrane separation has not been applied tosolvent exchange processes.

The present invention addresses the problems of the prior art.

In one aspect the present invention provides a process for carrying outa solvent exchange by altering the composition of an organic liquidcontaining at least one first solvent and at least one solute, toproduce a final organic liquid mixture in which the concentration of theat least one first solvent is reduced and the concentration of an atleast one second solvent has been increased, comprising the steps of:(a) providing a selectively permeable membrane having a first surfaceand a second surface; (b) transferring a portion of the first solventand optionally a portion of the at least one solute from the firstsurface to the second surface across the membrane by contacting theorganic liquid with the first surface, wherein the pressure at the firstsurface is greater than the pressure at the second surface, and whereinthe membrane is a selectively permeable membrane such that the membranerejection (R) of the at least one solute is greater than 0%; (c) addinga portion of at least one second solvent to the organic liquid retainedat the first surface of the membrane in step (b).

In a further preferred embodiment the organic liquid resulting from step(c) is further enriched in the second solvent relative to the firstsolvent through the steps of: (d) providing a selectively permeablemembrane having a first surface and a second surface; (e) transferring aportion of the first and second solvents and optionally a portion of theat least one solute from the first surface to the second surface acrossthe membrane by contacting the organic liquid from step (c) with thefirst surface, wherein the pressure at the first surface is greater thanthe pressure at the second surface, and wherein the membrane is aselectively permeable membrane such that the membrane rejection R of theat least one solute is greater than 0%; (f) adding a further portion ofthe at least one second solvent to the organic liquid retained at thefirst surface of the membrane in step (e).

By the term “selectively permeable” it is meant a membrane which willallow the passage of solvents while retarding the passage of solutes,such that a solute concentration difference can be produced by thesolvent flow across the membrane. The term selectively permeable may bedefined in terms of membrane rejection R, a common measure known bythose skilled in the art and defined as:

$\begin{matrix}{R = {\left( {1 - \frac{C_{Pi}}{C_{Ri}}} \right) \times 100\;\%}} & (1)\end{matrix}$where C_(P,i)=concentration of species i in the permeate, permeate beingthe organic liquid which has passed through the membrane, andC_(R,i)=concentration of species i in the retentate, retentate being theorganic liquid which has not passed through the membrane. It will beappreciated that a membrane is selectively permeable for a species ifR>0.

By the term “solute” it is meant an organic molecule with a molecularweight in the range 200-2000 Daltons which is present dissolved in atleast one solvent, such that the concentration of the solute in theresultant organic liquid mixture is less than 20 wt %.

By the term “solvent” it is meant an organic liquid with molecularweight less than 300 Daltons in which the solute can be dissolved to aconcentration of at least 0.1 wt %.

In a further aspect the present invention provides for carrying out asolvent exchange by omitting step (b), so that the at least one secondsolvent is added to the organic liquid prior to membrane filtration step(e).

In yet a further aspect the process may be carried out continuously sothat steps (b) and (c) or (e) and (D are performed simultaneously.

In yet a further aspect, the process may be carried out discontinuously.

In yet a further aspect, more than one selectively permeable membranemay be employed, so that the membranes used in steps (b) and (e), or inmultiple repeats of step (e), may be different. This allows the membraneto be chosen to provide the best combination of solvent flux and soluterejection for a specific composition of the organic liquid phase to becontacted with the membrane. By way of non-limiting example, wheretoluene is the first solvent to be exchanged for methanol as a secondsolvent, the membrane used for the first filtration step (b) may bechosen to provide a high toluene flux, while the membrane chosen for thesecond filtration step (e) may be chosen to provide a high methanolflux.

It is understood that the at least one first solvent may be replaced bya first mixture of solvents, or the at least one second solvent may bereplaced by a second mixture of solvents, or both first solvent andsecond solvent can be replaced by a first mixture of solvents and asecond mixture of solvents respectively, such that the first mixture ofsolvents and the second mixture of solvents vary in composition, withoutmaterially affecting the nature of the invention.

In yet further cases there may be more than one solute present in theorganic liquid, and more than one of these solutes may be retained atthe first surface of the membrane employed. In yet other cases, theremay be more than one solute present in the organic liquid, only some ofwhich are retained at the surface of the membrane.

We have found that in some cases during the membrane separation steps(b) or (e) the solute can attach itself loosely to the membrane surface.In these cases it can be readily washed off using fresh second solventprovided in the subsequent step (c) or (f). We have also found that insome cases during membrane separation steps (b) or (e) the solute canbegin to form crystals or other solids as solvent passes through themembrane and solute concentration in the retained liquid rises. In thesecases the solids may be re-dissolved in the fresh second solvent addedduring a subsequent step (c) of (f).

In yet a further preferred embodiment, the membrane may be backflushedusing either solvent or gas, to remove deposited material and improveflux.

In yet a further aspect, the invention may be applied to solventexchanges wherein the organic liquid mixture containing the firstsolvent and the solute result from an organic synthesis reaction andwherein it is desired to exchange solvents to a second solvent fromwhich the solute will be crystallised so as to purify the solutespecies.

In some cases it may be necessary to heat or cool the organic liquidprior to contact with the membrane in steps (b) or (e). For cases inwhich a crystallisation is employed following solvent exchange, it mayprove useful to heat the second solvent prior to steps (c) or (f), thusincreasing solute solubility, and then to subsequently decreasetemperature following steps (c) or (f) to effect crystallisation.

Preferably the solute will have a molecular weight of above 200 Daltons;yet more preferably above 300 Daltons, and yet more preferably above 400Daltons.

The solvents will be chosen with regard to solubility of solutes,viscosity, and miscibility with other solvents, among other factors suchas cost and safety. Suitable inert solvents are numerous and well knownto those skilled in the art. By way of non-limiting example, suitablesolvents include aromatics, alkanes, ketones, glycols, chlorinatedsolvents, esters, ethers, amines, nitrites, aldehydes, phenols, amides,carboxylic acids, alcohols and dipolar aprotic solvents, and mixturesthereof.

By way of non-limiting example, specific examples of solvents includetoluene, xylene, benzene, styrene, anisole, chlorobenzene,dichlorobenzene, chloroform, dichloromethane, dichloroethane, ethylacetate, methyl ether ketone (MEK), methyl iso butyl ketone (MIBK),acetone, ethylene glycol, ethanol, methanol, propanol, butanol, hexane,cyclohexane, dimethoxyethane, methyl tert butyl ether (MTBE), diethylether, adiponitrile, N,N dimethylfomamide, dimethyl sulfoxide, dioxane,nitromethane, nitrobenzene, pyridine, carbon disulfide, tetrahydrofuran,N-methyl pyrrolidone, acetonitrile, water, and mixtures thereof.

The membrane of the present invention can be configured in accordancewith any of the designs known to those skilled in the art, such asspiral wound, plate and frame, shell and tube, and derivative designsthereof. The membranes may be of cylindrical or planar geometry.

The membrane of the present invention may be a porous or a non-porousmembrane. Suitable membranes will have a rejection for the at least onesolute greater than 0%, yet more preferably greater than 40%, yet morepreferably greater than 70%, yet more preferably greater than 90% andyet more preferably greater than 99%.

The membrane of the present invention may be formed from any polymericor ceramic material which provides a separating layer capable ofpreferentially separating the solute from the solvent in steps (b) or(e). Preferably the membrane is formed from or comprises a materialselected from polymeric material suitable for fabricatingmicrofiltration, ultrafiltration, nanofiltration or reverse osmosismembranes, including polyethylene, polypropylene,polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF),polyethersulfone, polyacrylonitrile, polyamide, polyimide, celluloseacetate, and mixtures thereof. The membranes can be made by anytechnique known to the art, including sintering, stretching, tracketching, template leaching, interfacial polymerisation or phaseinversion. Yet more preferably the membrane is prepared from aninorganic material such as by way of non-limiting example siliconcarbide, silicon oxide, zirconium oxide, titanium oxide, or zeolites,using any technique known to those skilled in the art such as sintering,leaching or sol-gel processes.

In a preferred aspect the membrane is non-porous and the non-porous,selectively permeable layer thereof is formed from or comprises amaterial selected from modified polysiloxane based elastomers includingpolydimethylsiloxane (PDMS) based elastomers, ethylene-propylene diene(EPDM) based elastomers, polynorbornene based elastomers, polyoctenamerbased elastomers, polyurethane based elastomers, butadiene and nitrilebutadiene rubber based elastomers, natural rubber, butyl rubber basedelastomers, polychloroprene (Neoprene) based elastomers, epichlorohydrinelastomers, polyacrylate elastomers, polyethylene, polypropylene,polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF) basedelastomers, polyetherblock amides (PEBAX), and mixtures thereof.

In a preferred aspect the membrane comprises a reinforcing materialselected from an external mesh and support. This is particularlyadvantageous for homogenous tubes or sheets. Such tubes or sheets may bereinforced to increase their burst pressure, for example by overbraidingtubes using fibres of metal or plastic, or by providing a supportingmesh for flat sheets.

When the membrane comprises a non-porous layer and an additionalcomponent, the additional component may be a supporting layer. Thesupporting layer may be a porous support layer. Suitable materials forthe open porous support structure are well known to those skilled in theart of membrane processing. Preferably the porous support is formed fromor comprises a material selected from polymeric material suitable forfabricating microfiltration, ultrafiltration, nanofiltration or reverseosmosis membranes, including polyethylene, polypropylene,polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF),polyethersulfone, polyacrylonitrile, polyamide, polyimide, and mixturesthereof.

Selectively permeable membranes useful for the present invention aredisclosed in U.S. Pat. Nos. 5,205,934; 5,265,734; 4,985,138; 5,093,002;5,102,551; 4,748,288; 4,990,275; 4,368,112 and 5,067,970. Preferredmembranes are produced by WR Grace & Co and are described in U.S. Pat.No. 5,624,166 and WO 00/06293.

The rejection performance of the membrane may be found to be improved bypre-soaking the membrane in one or more of the solvents to be used inthe solvent exchange.

The process may be performed in a continuous, semi-continuous ordiscontinuous (batch mode) manner.

The process may be performed using dead-end or cross-flow filtration. Incases where dead-end filtration is used the pressure may be suppliedthrough a suitable pump or through a pressurizing gas, or through anyother device designed to exert pressure at the first surface of themembrane.

The portion of organic liquid removed during steps (b) and (e) may begreater than 30% of the starting organic liquid, preferably greater than50% of the starting organic liquid, yet more preferably greater than 70%of the starting organic liquid, even more preferably greater than 80% ofthe starting organic liquid

The invention will now be described, by way of example only, withreference to the accompanying drawings in which:

FIG. 1 is a schematic of an apparatus operating the process of thepresent invention,

FIG. 2 is a schematic of an apparatus operating the process of thepresent invention,

FIG. 3 shows graphs,

FIG. 4 shows graphs,

FIG. 5 shows graphs, and

FIG. 6 shows graphs.

FIG. 1 shows a schematic of one embodiment of the process. The organicliquid mixture containing the first solvent and dissolved solute is fed(1) to a pressure cell (4) containing a membrane (5), so that theorganic liquid mixture is contacted with the first surface of themembrane. Pressure is applied to the organic liquid through an inert gas(3). The organic liquid above the membrane is kept stirred using astirrer (2) to reduce fouling of the membrane surface. A portion of theorganic liquid passes through the membrane and exits the cell (6). Thesecond solvent is fed to the cell through line (7) via a pump (8). Asecond pump (10) removes organic liquid from the cell through line (9).The process can be operated with any of the flows through lines (1),(6), (7), (9) continuous, or discontinuous, and by removing andreapplying the pressure as required through line (3). The process inthis example is operated as a dead-end filtration process. In thisdead-end configuration it is possible to operate the process in batch sothat during each filtration stage a substantial fraction of solvent isforced out of the organic liquid mixture as permeate (6). This style ofoperation may lead to lower fluxes than the same configuration operatedcontinuously, as in the batch process the solute may tend to build up asa layer on the surface of the membrane as it becomes concentrated in theretentate. However, it will provide a solvent exchange to the samedegree as the continuous process while using less second solvent.

FIG. 2 shows another embodiment of the process. The organic liquidmixture containing the first solvent and the dissolved solute is fed(20) to a mixing tank (21) where second solvent is added (23). Theorganic liquid mixture is recirculated (24) by a pump (25) through amembrane module (26) containing a selectively permeable membrane (27). Aportion of the organic liquid permeates through the membrane under thepressure applied by the pump and exits the module (28). The organicliquid concentrated in solute (29) is returned to the mixing tank.Organic liquid containing the second solvent, small amounts of firstsolvent, and solute, is withdrawn from the mixing tank (22). The processin this example is operated as a cross-flow filtration process. In thisconfiguration it is possible to use the cross-flow velocity of themembrane to avoid the build-up of layers of solute on the surface of themembrane. Any or all of flows (20), (22), (23), (24) may be continuousor discontinuous.

FIG. 3 relates to Membrane Solvent Exchange of toluene for methanolusing STARMEM™ 122 as a membrane at 30 bar applied pressure, 20° C., andan initial concentration of 0.01 M TOABr. Rejection of TOABr wasmeasured as >99.9% for all filtration runs,

FIG. 4 relates to Membrane Solvent Exchange of methanol for ethyl;acetate using STARMEM™ 122 as a membrane at 30 bar, 20° C., and aninitial concentration of 0.01 M TOABr. Rejection of TOABr was measuredas >99.9% for all filtration runs,

FIG. 5 relates to Membrane Solvent Exchange of methanol for ethylacetate using STARMEM™ 122 as a membrane at 30 bar, 20° C., and aninitial concentration of 0.01 M TOABr. Rejection of TBABr was measuredas >99.5% for all filtration runs. Rejections for individual runs Rshown on plots below.

FIG. 6 relates to Membrane Solvent Exchange of methanol for ethylacetate using MPF50 as a membrane at 30 bar, 20° C., and an initialconcentration of 0.01 M TBABr. Rejection of TBABr is shown at base ofplot for each filtration run.

The invention will now be described in further detail in the followingnon-limiting Examples.

EXAMPLES Example 1

The solvent flux and rejection of various membranes is demonstrated inthis example. The solute is TetraOctylAmmoniumBromide (TOABr), MW=546Daltons. Membranes selected for this study are listed in Table 1,showing membrane properties:

TABLE 1 Membrane Properties (Manufacturer's Data) Membrane MW MembraneRejection Manufacturer type cutoff property (%) Koch MPF-50 700hydrophobic 70 (Sudan IV, (USA) MW = 384, in ethyl acetate) OsmonicsDesal-DK 350 hydrophilic 96 (Sucrose, (USA) MW = 342, in water) WR Grace142A 220 hydrophobic 62 (2% n-decane, (USA) MW = 142, in toluene) 142B200 hydrophobic 74 (2% n-decane, MW = 142, in toluene) MPF-50 andDesal-DK are available from membrane suppliers. WR Grace 142A and 142Bmembranes prepared using methods generally described in U.S. Pat. No.5,624,166 and WO 00/06293, both to WR Grace and Co.

Retention and fluxes were determined using an Osmonics/Desal (USA)SEPA-ST test cell Membrane discs were cut from A4 sheets in circulardiscs 49 mm in diameter, giving an active membrane area of 16.9 cm². Allexperiments were carried out in a fume cupboard. The cell waspressurised with compressed nitrogen gas at pressures of 5-50 bar. Thevolume of feed solution was 100 mL and the volume of permeate wasmeasured with a measuring cylinder. The solvent flux (J) was obtained by

$\begin{matrix}{J = \frac{V}{At}} & (2)\end{matrix}$where V is the volume of permeate (solvent), A is membrane area and t istime. This results in an “average” flux being arrived at—in generalfluxes were higher at the start of an experimental run than at the end.

All experiments were performed using a starting concentration of solute(TOABr) of 2 wt %. All toluene filtrations were at 20° C., all othersolvents at 30° C. 10 ml was retained as permeate in each filtration and90 ml withdrawn as permeate.

Results from these tests are shown in Table 2 below:

TABLE 2 Results for flux and rejection. Fluxes are measured in L m⁻² h⁻¹at 30 BarG. Solute Rejection of TOABr(R) is defined in equation (1).Ethyl Solvent Toluene Methanol Acetate Acetone Iso-propanol Membrane R(%) Flux R Flux R Flux R Flux R Flux 142A 99.8 34.9 99.8 25.4 100 43.7100 66.7 100 4.9 142B 99.7 48.6 99.9 19.7 100 57.3 99.9 114.4 — — DesalDK unstable 88.1 15.8 unstable unstable — — MPF50 96.5 87.7 — — — — — —97.4 15.1

Based on these results, each of these membranes is suitable for use withat least one solvent-solute combination.

Example 2

The overall solute recovery possible during a solvent exchange operationcarried out following the process of the invention is demonstrated inthis example. A solution of 2 wt % TOABr in toluene was used as aninitial organic liquid. A 100 ml sample of this organic liquid wasfiltered once using Membrane 1 so that 90 ml was withdrawn as permeateand 10 mL remained as retentate. To this 10 mL retentate, 90 mL of freshsecond solvent was added. The filtration of the resulting 100 mL oforganic liquid was carried out using Membrane 2 so that 90 mL waswithdrawn as permeate and 10 mL remained as retentate. 90 mL of freshsecond solvent was added to this retentate to provide a 100 ml finalorganic liquid containing TOABr solute. The recovery (W) of solute inthis fraction is defined as:

$W = {\frac{({FinalMassSoluteinSecondSolvent}\mspace{11mu})}{({InitialMassSoluteinFirstSolvent}\mspace{11mu})} \times 100\;\%}$The concentration of toluene in the final organic liquid was less than 1wt %. Data for solute recoveries (W) are shown in Table 3.

TABLE 3 Solute Recovery W (%) during solvent exchange from a firstsolvent (toluene in all cases) to a second solvent (as shown in Table).Solute is TOABr in all experiments. Second Solvent Membranes Ethyl Iso-Membrane 1 Membrane 2 Methanol Acetate Acetone Propanol 142A 142A⁽¹⁾96.9 98.8 98.8 98.8 142B 142B⁽¹⁾ 95.9 96.7 95.8 — 142A 142B 97.9 98.897.9 — 142B 142A 94.8 96.7 96.7 142A DK 46.3 — — — 142A MPF50 — — — 61.5142B MPF50 — — — 61.5 ⁽¹⁾Same membrane disc as used in first filtration.

Example 3

The process of solvent exchange is demonstrated in this example. Thesolutes are TetraOctylAmmoniumBromide (TOABr), MW=546 Daltons, andTetraButylAmmoniumBromide (TBABr) MW=322 Daltons. Membranes used areSTARMEM™ 122 supplied by W. R. Grace, and MPF-50 from Koch MembraneSystems (USA). STARMEM is a trademark of W. R. Grace.

Retention and fluxes were determined using an Osmonics/Desal (USA)SEPA-ST test cell Membrane discs were cut from A4 sheets in circulardiscs 49 mm in diameter, giving an active membrane area of 16.9 cm². Allexperiments were carried out in a fume cupboard. The cell waspressurised with compressed nitrogen gas at pressures of 5-50 bar. Thevolume of feed solution was 100 mL and the volume of permeate wasmeasured with a measuring cylinder. The solvent flux (J) was obtained by

$\begin{matrix}{J = \frac{V}{At}} & (2)\end{matrix}$where V is the volume of permeate (solvent), A is membrane area and t istime. This results in an “average” flux being arrived at—in generalfluxes were higher at the start of an experimental run than at the end.

The solvent exchanges from solvent 1 to solvent 2 were carried out asfollows:

-   (1) An initial 100 ml of starting solution containing solute at 0.01    M was concentrated to a retentate volume of 20 ml in the pressurised    membrane cell;-   (2) The membrane cell was depressurized, the 20 ml retentate was    made up to 100 ml by adding the solvent 2 and mixing well;-   (3) Repeat steps (1) and (2) until the purity of the second solvent    (measured using gas chromatography) is judged sufficient.

All filtration steps in this study were carried out at 30 bar appliedpressure and room temperature (around 20° C.).

Solvents, solutes and membranes employed are shown in Table 4 below:

TABLE 4 Solvent Exchanges Exchange Solvent 1 Solvent 2 Membrane Solute#1 toluene methanol STARMEM ™ 122 TOABr #2 methanol ethyl acetateSTARMEM ™ 122 TOABr #3 methanol ethyl acetate STARMEM ™ 122 TBABr #4methanol ethyl acetate MPF50 TBABrThe results are shown in FIGS. 3 to 6.

All publications mentioned in the above specification are hereinincorporated by reference. Various modifications and variations of thedescribed methods and system of the invention will be apparent to thoseskilled in the art without departing from the scope and spirit of theinvention. Although the invention has been described in connection withspecific preferred embodiments, it should be understood that theinvention as claimed should not be unduly limited to such specificembodiments. Indeed, various modifications of the described modes forcarrying out the invention which are obvious to those skilled inchemistry or related fields are intended to be within the scope of thefollowing claims.

1. A process for modifying a first organic composition resulting from anorganic synthesis reaction, said composition comprising (i) at least onefirst organic solvent having a molecular weight less than 300 daltons,(ii) at least one solute having a molecular weight between 200 and 2,000daltons, and (iii) at least one second organic solvent having amolecular weight less than 300 daltons that is distinct from said firstorganic solvent to produce a modified organic composition in which theconcentration of the at least one first organic solvent is reduced andthe concentration of the at least one second organic solvent isincreased, said method comprising the steps of: (a) providing aselectively permeable nanofiltration membrane having a first surface anda second surface; (b) transferring a portion of the first organicsolvent and optionally a portion of the solute from the first surface tothe second surface across the membrane by contacting the first organiccomposition with the first surface, wherein the pressure at the firstsurface is greater than the pressure at the second surface, and whereinthe membrane is a selectively permeable nanofiltration membrane suchthat the membrane rejection (R) of the solute is greater than 90%; (c)adding a portion of the second organic solvent to the organiccomposition retained at the first surface of the membrane; (d)transferring a portion of the first and second organic solvents andoptionally a portion of the solute from the first surface to the secondsurface across the membrane by contacting the organic composition fromstep (c) with the first surface, wherein the pressure at the firstsurface is greater than the pressure at the second surface; and (e)repeating the steps of adding the second organic solvent and contactingthe organic composition with the selectively permeable nanofiltrationmembrane under pressure until the final concentration of the firstsolvent in the organic composition is reduced below a pre-determinedvalue relative to the concentration of the second solvent in the organiccomposition.
 2. A process according to claim 1 in which more than oneselectively permeable nanofiltration membrane is used for consecutivemembrane filtration stages, wherein said membranes are selectivelypermeable nanofiltration membranes such that the membrane rejection (R)of the solute is greater than 90%.
 3. A process according to claim 1 inwhich the first organic solvent is a first mixture of solvents.
 4. Aprocess according to claim 1 in which the second organic solvent is asecond mixture of solvents distinct from the first organic solvent.
 5. Aprocess according to claim 1 in which there is more than one solutepresent in the organic composition which is retained at the surface ofthe membrane.
 6. A process according to claim 1 in which there is morethan one solute present in the organic composition which is retained atthe surface of the membrane, and in which at least one solute is notretained at the surface of the membrane.
 7. A process according to claim1 which at least one solute present in the organic composition attachesitself to the membrane or otherwise precipitates out of the compositionduring a filtration step, and is re-dissolved by addition of the secondsolvent.
 8. A process according to claim 1 wherein at least one organicsolute is separated from the organic composition produced from theprocess by crystallization.
 9. A process according to claim 1 in whichthe solute has a molecular weight above 200 Daltons.
 10. A processaccording to claim 1 in which the solute has a molecular weight above300 Daltons.
 11. A process according to claim 1 in which the solute hasa molecular weight above 400 Daltons.
 12. A process according to claim 1in which the first or second organic solvents are independently selectedfrom the group consisting of aromatics, alkanes, ketones, glycols,chlorinated solvents, esters, ethers, amines, nitriles, aldehydes,phenols, amides, carboxylic acids, alcohols and dipolar aproticsolvents, and mixtures thereof, and in which the second organic solventis distinct from the first organic solvent.
 13. A process according toclaim 1 in which the first or second organic solvents are independentlyselected from the group consisting of toluene, xylene, benzene, styrene,anisole, chlorobenzene, dichlorobenzene, chloroform, dichloromethane,dichloroethane, ethyl acetate, methyl ether ketone (MEK), methyl isobutyl ketone (MIBK), acetone, ethylene glycol, ethanol, methanol,propanol, butanol, hexane, cyclohexane, dimethoxyethane, methyl tertbutyl ether (MTBE), diethyl ether, adiponitrile, N,N dimethylformamide,dimethyl sulfoxide, dioxane, nitromethane, nitrobenzene, pyridine,carbon disulfide, tetrahydrofuran, N-methyl pyrrolidone, acetonitrile,water, and mixtures thereof, and in which the second organic solvent isdistinct from the first organic solvent.
 14. A process according toclaim 1 in which the selectively permeable nanofiltration membrane hascylindrical or planar geometry and is configured as spiral wound, plateand frame, shell and tube, or derivative designs thereof.
 15. A processaccording to claim 1 where one or more of the membrane separation stepsis operated in a dead-end filtration mode.
 16. A process according toclaim 1 where one of more of the membrane separation steps is operatedin a cross-flow filtration mode.
 17. A process according to claim 1 inwhich the selectively permeable nanofiltration membrane separatessolutes with molecular weights greater than 200 Daltons from solventswith molecular weights less than 200 Daltons.
 18. A process according toclaim 1 in which the selectively permeable nanofiltration membraneseparates solutes with molecular weights greater than 300 Daltons fromsolvents with molecular weights less than 300 Daltons.
 19. A processaccording to claim 1 in which the selectively permeable nanofiltrationmembrane is formed from a polymeric or ceramic material.
 20. A processaccording to claim 1 wherein the membrane consists essentially of apolyimide polymer based on any of the following: (i) a polymer based on5(6)-amino-1-(4′-aminophenyl)-1,3-trimethylindane and benzophenonetetracarboxylic acid; (ii) a polymer with 1 (or3)-(4-aminophenyl)-2,3-dihydro-1,3,3 (or1,1,3)-trimethyl-1H-inden5-amine and5,5′-carbonylbis-1,3-isobenzofurandione; (iii) a copolymer derived fromthe co-condensation of benzophenone 3,3′,4,4′-tetracarboxylic aciddianhydride and a mixture of di(4-aminophenyl) methane and toluenediamine of the corresponding diisocyanates, 4,4′-methylenebis(phenylisocyanate) and toluene diisocyanate; or (iv) a copolymer derived fromthe co-condensation of 1 H,3H-Benzo[1,2-c: 4,5-c′]difuran1,3,5,7-tetrone with 5,5′-carbonylbis[1,3-isobenzofurandione],1,3-diisocyanato-2methylbenzene and 2,4-diisocyanato-1-methylbenzene.21. A process according to claim 1 in which the selectively permeablenanofiltration membrane is a composite membrane.
 22. A process accordingto claim 1 in which the membrane is nonporous and is formed from orcomprises a material selected from the group consisting of modifiedpolysiloxane based elastomers including polydimethylsiloxane (PDMS)based elastomers, ethylene-propylene diene (EPDM) based elastomers,polynorbornene based elastomers, polyoctenamer based elastomers,polyurethane based elastomers, butadiene and nitrile butadiene rubberbased elastomers, natural rubber, butyl rubber based elastomers,polychloroprene (Neoprene) based elastomers, epichlorohydrin elastomers,polyacrylate elastomers, polyethylene, polypropylene,polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF) basedelastomers, and mixtures thereof.
 23. A process according to claim 1wherein the membrane comprises a reinforcing material selected from anexternal mesh and support.
 24. A process according to claim 1 whereinthe membrane is a composite membrane comprising a porous support and atleast one non-porous layer.
 25. A process according to claim 1 whereinthe process is performed in a continuous manner.
 26. A process accordingto claim 1 wherein the process is performed in a discontinuous manner.27. A process according to claim 1 wherein the membrane is pretreated bysoaking in a constituent of the organic composition prior to use.
 28. Aprocess according to claim 1 wherein backflushing of the membrane usingeither solvent or gas is used to improve membrane flux.